The role of RNA uptake in platelet heterogeneity
The role of RNA uptake in platelet heterogeneity
复制标题
DOI：
10.1160/th16-11-0873
复制
发表时间：
2017-05-01
影响因子：
6.7
通讯作者：
Freedman, Jane E.
中科院分区：
文献类型：
--
作者：
Clancy, Lauren;Beaulieu, Lea M.;Freedman, Jane E.
血小板在调节血管稳态中的作用已经扩展到止血和血栓形成的调解之外。血小板RNA的发现和含有不同量RNA的血小板亚群的存在表明血小板转录物在血管功能中的作用。由于无核血小板中的RNA具有生物学功能，并且可以转移到其他血管细胞，因此我们假设血小板RNA在血小板的寿命期间随着水平细胞转移导致的血小板大小减小而减少。本研究的目的是确定血小板RNA变异是否是血小板和其他血管细胞之间水平细胞转移的结果。利用血小板分选和RNA测序，我们发现较小的血小板比较大的血小板含有更多样化的转录本。使用荧光成像、基因表达分析以及体外和体内建模的进一步研究显示，血小板以复杂的方式从其他血管细胞摄取RNA，揭示了血小板通过双向RNA转移在调节血管稳态中的动态作用。由此产生的RNA谱异质性表明血小板依赖于大小和复杂性的独特功能作用。这项研究扩展了我们对血小板功能和异质性的基本理解，并且是第一个评估内源性血管RNA吸收及其与血小板过程的关系的研究。我们的研究结果描述了一种新的内源性现象，可以帮助阐明血小板在这些非血栓形成和止血领域的作用，以及目前的诊断和治疗发展的潜力。
The role of platelets in regulating vascular homeostasis has expanded beyond mediation of haemostasis and thrombosis. The discovery of platelet RNA and the presence of subpopulations of platelets containing varying amounts of RNA suggest a role for platelet transcripts in vascular function. As the RNA in anucleated platelets is biologically functional and may transfer to other vascular cells, we hypothesised that platelet RNA diminishes over the lifespan of the platelet with diminishing platelet size due to horizontal cellular transfer. The purpose of this study is to determine if platelet RNA variance is the result of horizontal cellular transfer between platelets and other vascular cells. Utilising platelet sorting and RNA sequencing, we found that smaller platelets contained a more diverse set of transcripts than larger platelets. Further investigation using fluorescence imaging, gene expression analyses and in vitro and in vivo modelling revealed that platelets take up RNA from other vascular cells in a complex manner, revealing a dynamic role for platelets in modulating vascular homeostasis through bidirectional RNA transfer. The resultant RNA profile heterogeneity suggests unique functional roles for platelets dependent on size and complexity. This study expands our basic understanding of platelet function and heterogeneity and is the first to evaluate endogenous vascular RNA uptake and its relation to platelet processes. Our findings describe a novel endogenous phenomenon that can help elucidate the platelet's role in these non-thrombotic and haemostatic fields, as well as present potential for diagnostic and therapeutic development.